Study to Prevent Cartilage Damage Following Acute Knee Injury.

May 29, 2013 updated by: Duke University

IL-1ra for Prevention of Chondropathy Following Knee Injury

Individuals who have had a severe knee injury have an increased risk of developing arthritis of the knee and at a much earlier age than would otherwise be expected. The swelling and inflammation that occur after injury are believed to be responsible for this cartilage damage. The cartilage (material that provides a cushion in the knee) is the primary protection from what is called degenerative arthritis or osteoarthritis. We hope to reduce this swelling and prevent the damage to cartilage that occurs after injury by injecting a medication that blocks one of the proteins responsible for inflammation and cartilage breakdown. This protein is called interleukin-1 and can be inhibited by an interleukin-1 receptor antagonist called anakinra. Anakinra will be injected directly into the injured knee and response to the injection will be measured by symptoms and analysis of cartilage breakdown in the knee fluid and blood.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Osteoarthritis is highly prevalent with significant impact on health care utilization and personal suffering. Injury predisposes to OA even after surgical correction (1, 2). Definitive therapy for established OA is lacking and current treatments are increasingly questioned with regard to long-term safety. Interleukin-1 is instrumental in OA pathogenesis (3-5). Recent studies by Chevalier demonstrated that intra-articular use of IL-1ra was safe in patients with established OA (6). We hope to show that IL-1ra will provide symptomatic benefit after knee injury as well as decreasing cartilage breakdown.

The trial will consist of trial administering 150mg of Anakinra, or placebo, within 30 days of an acute knee injury that requires surgical repair. We hypothesize that higher IL-1 in synovial fluid after injury will predict greater symptomatic response to IL-1ra. Outcome measures will be functional and pain assessments at regular intervals before and after surgery (7, 8). Cartilage catabolism will be assessed with two primary measures. First we will assess degree of chondropathy via direct cartilage visualization and scoring at the time of arthroscopic repair (9). Secondly, the impact of IL-1ra on the inflammatory milieu will be determined through analysis of serum and synovial fluid cytokine levels and cartilage biomarkers at enrollment and again at the time of surgical repair.

The impetus for this study is based on previous work done in animal models of OA, showing prevention of cartilage damage following surgically induced ACL injury (10-12). We believe that intra-articular delivery of anakinra within a short time following knee injury will improve patient function and pain reporting and will also prevent chondropathy that results from injury.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Sports Medicine Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 30 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Onset of injury less than 4 weeks prior to evaluation
  • Severe knee injury that requires surgery, including anterior cruciate ligament tear, meniscus tear and chondral injury
  • BMI less than 30
  • Age 18-30
  • Women will have serum pregnancy testing (bHCG) at time of entry and on follow-up evaluation and must agree to use an approved form of contraception during the study period.

Exclusion Criteria:

  • Prior signal joint injury requiring medical evaluation
  • History of arthritis or rheumatic disease
  • History of intra-articular corticosteroid in index joint
  • Septic joint
  • Evidence of chronic joint disease by plain radiograph
  • Fracture or multiple ligament tear
  • Pregnancy or lactation
  • Inability to give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Intra-articular IL-1Ra
Drug: Anakinra
150 mg IL1Ra ia x1 vs saline ia x1
Other Names:
  • Kineret
Placebo Comparator: 2
Intra-articular saline
Drug: Anakinra
150 mg IL1Ra ia x1 vs saline ia x1
Other Names:
  • Kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
pain
Time Frame: 4 and 30 days
4 and 30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
chondropathy score
Time Frame: 30-60 days
30-60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Investigators

  • Study Chair: Virginia B Kraus, MD, PhD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

May 30, 2006

First Submitted That Met QC Criteria

May 30, 2006

First Posted (Estimate)

June 1, 2006

Study Record Updates

Last Update Posted (Estimate)

May 30, 2013

Last Update Submitted That Met QC Criteria

May 29, 2013

Last Verified

January 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00014439
  • 7939-05-11 (Other Identifier: Duke IRB#)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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